3-keto-d-pentonic acid lactone and process for the manufacture of same



Pa tented Declj13, 1 938 g the two theoretically possible :forms of the.3-KETO-D-PENTONIO ACID, LACTONE AND- rnoonss FOR THE MANUFACTURE or.SAME

Tadeus Beichstein, zurich switzerland, assignor to Hoffmann-La RocheInc, Nutley, N. J a corporation of New Jersey No Drawing. ApplicationApril 10, 1937, Serial No. 136,229. In Switzerland March 12,193?

g 9 Claims. 5 (01. 2605-344) (c=1 in 0.01 n-hydrochloric acid).

The comlactone of 3"-keto-pentonic acid, i. elthe.dextroand'laevo-forms, only the laevo-form, is ':so far known..(Helvetica Chimica Acta 1'7, 1934, pageg It has now been'found that theparticularly valuable 3-keto-d-pentonic acid lactone can be readily'obtained in good yield from derivatives of d-xylosonic acid and dribosonic a'cid capable of 10 being hydrolized by acids by heatingin, orletting the compounds stand for some time at room temperature in, anacid medium.

, As starting materials the salts, esters, methyl ene-ether derivativesand alkyl-lactolides of the 15 two acids can be used. It is particularlyadvantageous to heat with an excess of alcoholic hydrochloric acid asthis enables the reaction-prodnot to be easily isolated. But sulphuricacid, tol- -',uene-sulfonic acid and the like, as well as purely 20organic acids are also suitable for this purpose. n For therearrangement of free mono-methyleneether-d xylosonic acids,'an additionof acid is not even necessary. Such an addition only accelerates thereaction which takes place when the 25 temperature is raised. Dioxaneand other ethers can be used as solvents. Mixtures of alcoholichydrochloric acid and an indifferent solvent, such as'b'enzene,chloroform etc.,are also very suitable. fThe reaction can be formulatedas follows:

OOOH CH=O\(JOOH 7 2" f -C H OH: 35 OOH CH; /O\ .L H-COH I H 0 on.

' on, -OH:

, Mono-'acetone- Mothyl-lactolide d-xylosonlc of mono-acetone- 4 acidd-ribosonic acid m (Formula 1) I (Formula 2) (30- (|JO OH(|l--H OH -OC=O OH- 45 l l H- H(lJ- OHIOH CHIOH I V 3-keto-d-pentonic 5o acidlactone (Formula 3) i V The 3-keto-d-penton'ic acid lactone crystallizesinneedles' melting at 156 0., its specific rotation pound is veryreadily soluble in water, methanol, alcohol and acetone, soluble indioxane, moderately in ethyl-acetate, only slightly soluble in ether andbenzene and practically insoluble in petroleum-ether. It is completelyanalogous in its reducing action tothe well-known ascorbic acid. Theaqueous solution prepared at 0 C. rapidly neutralizes one molecule ofalkali, while at a somewhat higher temperature, or when theneutralization is carried out more slowly, more alkali is neutralized.The 3-keto-d-pentonic acid lactone possesses a very high anti-scorbuticactivity and is to be used as a medicine.

- d-xylosonate are boiled for 5 hours with 200 parts by ,weight of 4%alcoholic hydrochloric acid under a reflux-condenser. The product isseparated'fr'om the potassium-chloride formed and the solutionevaporated in vacuo. The residue is recrystallized from ethyl-acetate.The 3-ketod-pentonic acid lactone is obtained in well-developedcrystals.

Exa'mple 2 1 part by weight of acetone-Z-keto-d-ribonic acidmethyl-lactolide is dissolved in parts of water. Then 0.5 part by weightof Z-n-hydrochloric acid are added and the solution heated on thewater-bath for one hour, air being excluded by introducing a current ofcarbon-dioxide. The solution is now evaporated in vacuo, the

residue dissolved in alcohol and precipitated with alcoholiclead-acetate. The lead-acetate precipitate is suspended in watersaturated with carbondioxide, treated with hydrogen-sulfide in the coldand. the solution sucked off from the leadsulflde and evaporated to asirup in vacuo. For purification, the residue is dissolved in littleacetone, treated with pure ethyl-acetate and the greater part of theacetone removed by distillation. On inoculating the clear solution, the3- keto-d-pentonic acid lactone crystallizes.

Example 3 flux-condenser. When the reducing action of a test-portion of5 cc. no longer increases on further heating the solution is evaporatedin vacuo and the residue recrystallized from ethyl-acetate.

I claim:

1. Process for producing 3-keto-d-pentonic acid lactone, which comprisestreating a substance selected from the group consisting of carboxylicacid esters, carboxylic acid salts, methylene ethers, methylene ethercarboxylic acid salts, and methylene ether carboxylic acid esters ofd-xylosonic acid, which is capable of being hydrolyzed in an acid mediumwith an acid. 7

stance selected from the group consisting of carboxylic acid esters,carboxylic acid salts, methylene ethers, methylene ether carboxylic acidsalts; and methylene ether carboxylic acid esters of d-Xylosonic acid,which is capable of being hydrolyzed in an acid medium with an acid.

LProcess for producing S-keto-d-pentOnic acid lactone,-which comprisestreating a substance selected from the 'group consisting of carboxylicacid esters, carboxylic acid salts, methylene ethers, methylene ethercarboxylic acid salts, andmethylene ether carboxylic acid esters ofd-xylosonic acid, which is capable of being hydrolyzed in an acid mediumwith an acid in an organic solvent in substantial absence of water.

5. Process for producing 3-keto-d-pent0nic acid lactone, which comprisestreating a sub stance selected from the group consisting of carboxylicacid esters, carboxylic acid salts, methylene ethers, methylene ethercarboxylic acid salts, and methylene ether carboxylic acid esters ofd-xylosonic acid, which is capable of being hydrolyzed in an acid mediumwith an acid in an indiiferent solvent in substantial absence of water.

6. Process of producing 3-keto-d-pentonic acid lactone which comprisestreating potassium mono-acetone-d-xylosonate with hydrochloric acid.

7. Process of producing 3-keto-d-pentom'c acid lactone which comprisestreating potassium mono-acetone-d-xylosonate with hydrochloric acid in adiluent. I

8. Process of producing 3-keto-d pentonic acid lactone which comprises.treating potassium mono-acetone-d-Xylosonate with alcoholichydrochloric acid.

9. Process of producing 3-keto-d-pentonic acid lactone which comprisesheating potassium mono-acetone-d-Xylosonate'with alcoholic hydrochloricacid."

.TADEUS REIVCHSTEIN. 7

